The primary goal of this study is to assess the elimination pharmacokinetics and metabolic disposition of cocaine in a population of chronic cocaine users. Several reports suggest a prolonged elimination of cocaine and metabolites after chronic use compared to single or occasional use. This study was designed to measure the half-lives of cocaine in plasma and saliva of individuals who consume cocaine on a frequent basis. We investigated the disposition and elimination patterns of cocaine and metabolites in the body fluids of chronic high-dose cocaine users during acute cessation of use. Plasma and saliva specimens were collected over a 12 h period during cessation and analyzed by gas chromatography-mass spectrometry. Pharmacokinetic parameters were derived by noncompartmental analysis of plasma and saliva data. Results indicated a cocaine terminal T1/2 of 3.8 hours in plasma and 7.9 hours in saliva. The terminal T1/2 of benzoylecgonine was 6.6 hours in plasma and 9.2 hours in saliva. Compared with prior studies of acute low-dose cocaine administration, these findings suggest that cocaine's half-life is longer in active street users than in occasional users though the half-life of its main metabolite benzoylecgonine remains similar (as do cocaine saliva-to-plasma ratios). Thus, regular use of cocaine appears to alter the disposition and elimination of cocaine when compared to single or occasional use. In a more recent analysis we reported urinary excretion patterns of cocaine metabolites as benzoylecgonine (BE) equivalents from 18 of the same individuals, housed for up to 14 days on a closed research unit. In addition, we evaluated whether creatinine normalization of BE equivalents increased mean detection time and reduced mean within-subject variability. All urine voids (N=953) were individually assayed; BE equivalents were determined semi-quantitatively by FPIA (TDx, Abbott Laboratories, Abbott Park, IL). Compared to concentration in first void after admission, BE equivalents decreased to approximately 33%, 8%, and 4% at 24, 48, and 72 hours, respectively. Mean + SD (range) time to first negative specimen (BE equivalents <300 ng/mL) was 43.6 +/- 17.1 (16-66) hours. BE equivalents fluctuated considerably across successive specimens; 69% of participants tested positive at least once after testing negative, and the mean time to last positive specimen was 57.5 + 31.6 (11-147) hours after the first specimen. Thus, mean cocaine metabolite detection times were consistent with prolonged elimination, with 63% of participants testing positive longer than the expected 48-hour window of detection after admission to the unit. Mean time to last positive after last use of cocaine, known by self-report only, was approximately 81 +/- 34 [range 34 - 162] hours. Creatinine normalization, with the cutoff of 300 ng BE equivalents/mg creatinine, increased detection time: mean time to first negative specimen was 54.8 +/- 20.7 (20-100) hours, and mean time to last positive specimen was 88.4 +/- 51.0 (35.6-235) hours. Compared to concentration in the first void after admission, BE equivalents/creatinine decreased to approximately 56%, 6%, and 5% at 24, 48, and 72 hours. However, creatinine normalization did not reduce the fluctuation of BE equivalents across successive specimens. Thus, creatinine normalized values may be useful when the goal is to maximize the probability or duration of cocaine metabolite detection, but may be less useful in determining whether an individual has used cocaine since a previous specimen collection. We are planning to examine both cocaine and methadone disposition in the outpatient group.